Hepatitis C Virus Infection
Conditions
Brief summary
Hepatitis C virus (HCV), which infects more than 185 million people, is a major risk factor. Direct-acting antiviral (DAA) therapy has significantly improved the eradication of the virus, but has not completely eliminated the risk of HCC, so careful surveillance is necessary. The genetic diversity of the natural killer receptor, histocompatibility antigens (HLA) and interferon lambda 4 (INFL4) activity, among other factors, have been found to be crucial in directing disease progression. Importantly, these markers are detectable years before the diagnosis of HCC. In addition, polymorphic variants attributable to the expression of genes involved in innate-type immune response, such as IFNL4 and HLA-E, have been shown to be predictive for the development of HCC and have not yet been extensively studied. The aim of the study is to evaluate novel circulating biomarkers, including the presence of antibodies to specific HCV proteome peptides, IFNL4 expression, and the interaction of specific HLA receptors/ligands in a large cohort of HCV-positive subjects in order to create a screening strategy for the early diagnosis of HCV-associated HCC. Part of the study will be devoted to describing the immune microenvironment associated with the expression of IFNL4 and HLAE, evaluating them as potential prognostic indicators for HCC in HCV-infected subjects undergoing surgery for HCC, as well as in those with advanced/metastatic HCC.
Interventions
None listed
Sponsors
Centro di Riferimento Oncologico - Aviano
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients aged ≥18 years with the presence of chronic infection, fibrosis, cirrhosis or HCV- associated HCC * Patients able to understand and willing to sign the of informed consent * Patients to answer the questions in the questionnaire of enrollment
Exclusion criteria
* Treatment for other oncological diseases * Immunodepression congenital or acquired (HIV, organ transplantation, pharmacological)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in antibody profile between subjects with and without chronic HCV infection | up to 2 years | Mean or median difference between the groups, as appropriate, will be calculated |
| Difference in antibody profile between subjects with chronic HCV infection receiving or not receiving DAA therapy | up to 2 years | Mean or median difference between the groups, as appropriate, will be calculated |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterization of Interferon Lambda 4 (INFL4) and Human Leukocyte antigene (HLA-E) variants within patient with or without HCV related hepatocarcinoma (HCC) | up to 2 years | Frequencies of genetic variants within patient with or without HCV related hepatocarcinoma (HCC) will be reported |
| Define a relationship between IgG levels toward HCV-specific peptides and viral load/development clinical after 2 years of follow-up | up to 2 years | Correlation coefficient between the highest IgG levels towards at least one specific HCV peptide and high viral load will be calculated |
| Define the mRNA pathways activated in the subjects with expression of INFL4 and of HLA-E | up to 2 years | Data will be illustrated with volcano plot and heat map |
| Characterization of INFL4 and HLA-E variants within patient with or without HCV related chronic hepatitis | up to 2 years | Frequencies of genetic variants within patient with or without HCV related chronic hepatitis will be reported |
| Define a relationship between IgG levels toward HCV-specific peptides and HCV genotype | up to 2 years | Relation will be analyzed with logistic regression analysis and represented with Odds Ratio (OR) and relative 95% Confidence Interval (95% CI) |
Countries
Italy
Contacts
Primary ContactValli De Re, PhD
Outcome results
None listed